Previous studies have demonstrated that mice differing only in the set of genes in the major histocompatibility complex (MHC) produce odors which other mice are able to differentiate. We have now found that at least one source for odors differentiating MHC-dissimilar mice is urine. Mice were trained, in a Y maze, to discriminate urines collected from panels of inbred mice differing only at the MHC. Successful training was also accomplished using F2 segregants indicating that the train of distinctive urine odor segregates with MHC type. Control studies showed that the MHC discrimination could not be explained by artifact or non-genetic incidental variation. These differences in urine odors are presumed to be implicated in the previously described dependence of mating preference on MHC type. Studies are continuing aimed at: (1) investigating the ability of different subregions within MHC to produce distinctive urinary odors; (2) chemically characterizing differences in urines of MHC-dissimilar mice; and (3) evaluating the role of MHC difference in males and their odors in the maintenance of female pregnancy. These studies provide a link between immunity and olfaction, two biological systems which are similar in exhibiting a vast range of precise chemical recognition.